AI 靶点发现临床研究International journal of molecular sciences
A Mechanistic Map of the Phenotypic Complexity in Recessive Dystrophic Epidermolysis Bullosa Provides Basis for Therapeutic Target Discovery and Drug Repurposing.
Sara Herráiz-Gil、Miriam Payá-Milans、María Del Carmen de Arriba、Lucía Martínez-Santamaría、Carlos Loucera、Nuria Illera、Marcela Del Río、Joaquín Dopazo、Carlos León、María José Escámez
作者机构
Departamento de Bioingeniería, Universidad Carlos III de Madrid, ROR Code 03ths8210, Avenida de la Universidad, 30 (Edificio Sabatini), 28911 Leganés, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), 28029 Madrid, Spain.
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), 28040 Madrid, Spain.
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, 28040 Madrid, Spain.
Platform for Computational Medicine, Andalusian Public Foundation Progress and Health-FPS, 41092 Seville, Spain.
Computational Systems Medicine, Institute of Biomedicine of Seville (IBIS), Hospital Virgen del Rocío, 41013 Seville, Spain.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: shisi@fudanpci.org.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China.
Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: xujin@fudanpci.org.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address: yuxianjun@fudanpci.org.
Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Hong Kong, China.
Department of Pathology, Jiangmen Central Hospital, Jiangmen, China.
Department of Pathology, Zhongshan People's Hospital, Zhongshan, China.
Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Department of Pathology, The Tenth Affiliated Hospital, Southern Medical University, Dongguan People's Hospital, Dongguan, China.
Department of Pathology, Huizhou Central People's Hospital, Huizhou, China.
Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Hong Kong, China. jhc@ust.hk.
Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong, China. jhc@ust.hk.
Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. jhc@ust.hk.
HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute, Futian, Shenzhen, China. jhc@ust.hk.
State Key Laboratory of Nervous System Disorders, The Hong Kong University of Science and Technology, Hong Kong, China. jhc@ust.hk.
SIAT-HKUST Joint Laboratory for Brain Science, The Hong Kong University of Science and Technology, Hong Kong, China. jhc@ust.hk.
Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. caimy@sysucc.org.cn.
Vincent J Straub、Stefania Benonisdottir、Giovanni Scotti Bentivoglio、Neil Wary、Robert Campbell、Augustine Kong、Melinda C Mills
作者机构
Leverhulme Centre for Demographic Science, Nuffield Department of Population Health, University of Oxford and Nuffield College, Oxford, UK. vincent.straub@ndph.ox.ac.uk.
Leverhulme Centre for Demographic Science, Nuffield Department of Population Health, University of Oxford and Nuffield College, Oxford, UK.
Institute of Physical Sciences, University of Iceland, Reykjavík, Iceland.
Department of Economics, Econometrics and Finance, University of Groningen, Groningen, the Netherlands.
Leverhulme Centre for Demographic Science, Nuffield Department of Population Health, University of Oxford and Nuffield College, Oxford, UK. melinda.mills@demography.ox.ac.uk.
Department of Economics, Econometrics and Finance, University of Groningen, Groningen, the Netherlands. melinda.mills@demography.ox.ac.uk.
Department of Genetics, University Medical Centre Groningen, Groningen, the Netherlands. melinda.mills@demography.ox.ac.uk.
Shengxin Zhang、Keqin Tan、Qin Zhang、Yuzhe Zhao、Ziyang Cheng、Xinggang Yang、Jingsi Dong、Jiaming Liu、Xuelei Ma
作者机构
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Postgraduate Students, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Hematology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China. dongjingsi@wchscu.edu.cn.
Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. dongjingsi@wchscu.edu.cn.
Department of Urology, West China Hospital, Sichuan University, Chengdu, China. JM3099@163.com.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China. maxuelei0726@wchscu.cn.
Fei Liu、Kai Wang、Hui Xu、Cheng Tang、Xian Shen、Meihao Wang、Lei Yang、Li Yang、Li Liu、Changxi Hu、Gen Li、Wei Wu、Zixing Zou、Bingzhou Li、Sian Liu、Jin Kang、Jungho Kong、Ting Li、Io Nam Wong、Xiaoying Huang、Gang Chen、Wenyang Lu、Ian Ziyar、Charlotte L Zhang、Yiwen Sun、Weihong Lin、Caiwen Ou、Manson Fok、Taiwa Hou、Winston Wang、Kanmin Xue、Yun Yin、Hao Zhu、Jonathan Gootenberg、Omar O Abudayyeh、Michael Karin、Alexandre Loupy、John E J Rasko、Trey Ideker、Huiyan Luo、Eric Oermann、Kang Zhang、International Consortium of Digital Twins in Healthcare and Medicine
作者机构
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Department of Urology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Department of General Surgery, Department of Hepatobiliary Surgery, Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Radiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Intelligent Medical Imaging of Wenzhou, Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Orthopedics, Key Laboratory of Hepatosplenic Surgery of Ministry of Education, the First Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Respiratory and Critical Care Medicine, Center for Big Data and Intelligent Medicine, the First Affiliated Hospital of Chongqing Medical University, Key Laboratory of Digital Health and Intelligent Medicine, Chongqing Municipal Health Commission, Chongqing Translational Medicine Center, Chongqing, China.
Department of Health Management, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Big Data and Biomedical AI, College of Future Technology, Peking University, Peking-Tsinghua Center for Life Sciences, Beijing, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China.
Departments of Medicine and Bioengineering, Moores Cancer Center, School of Medicine, UC San Diego, CA, USA.
Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdisciplinary and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, China.
Nepean Hospital, Sydney, Australia.
Key Laboratory of Intelligent Medical Imaging of Wenzhou, Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Dongguan Hospital, Southern Medical University, Guangzhou, China.
Conde S. Januario Hospital, Macau, China.
Department of Internal Medicine, Mayo Clinic, Arizona, USA.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Faculty of Health and Wellness, Faculty of Business, City University of Macau, Taipa, Macau SAR, China.
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Gene and Cell Therapy Institute, Mass General Brigham, Cambridge, MA, USA.
Université Paris Cité, INSERM U970 PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France; Department of Kidney Transplantation, Assistance Publique - Hôpitaux de Paris, Paris, France.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
Departments of Medicine and Bioengineering, Moores Cancer Center, School of Medicine, UC San Diego, CA, USA; Big Data Institute, Oxford University, Oxford, UK.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Departments of Neurosurgery, Radiology, and Data Science, Neuroscience Institute, NYU Langone Medical Center, New York University, New York, NY, USA.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: kang.zhang@gmail.com.
技术路线
3.67 million individuals/17.7 million clinical visits (COMPASS cohort, longitudinal EHR + chest X-ray) → Oncoformer unified multimodal transformer analysis → validation on independent external cohorts including UK Biobank, with staging independently validated against postoperative pathological endpoints and convergence on core cancer genomic pathways
为什么值得关注
AI 辅助短评，基于标题和摘要整理本研究针对RDEB表型高度异质、缺乏可操作分子模型的问题，基于患儿皮肤转录组构建首個功能性机制图谱，结合机器学习推断靶点并重定位药物。其价值在于将疾病回路与炎症、纤维化、肿瘤进展等标志关联，为靶点发现和已批准药物重定位提供系统依据。